This report presents an otherwise healthy infant who developed unexplained apnea and long-segment Hirschsprung disease. After extensive evaluation that included a paired-like homeobox 2b gene (PHOX2B) analysis, he was found to have Haddad syndrome, a congenital disorder that features central congenital hypoventilation syndrome in conjunction with Haddad syndrome. Recent work has associated polyalanine repeats within the PHOX2B gene on chromosome 4p12 with central congenital hypoventilation syndrome, whereas PHOX2B knockout mice develop aganglionic bowels.
Paton JY, Swaminathan S., Sargent CW et al. Ventilatory response to exercise in children with congenital central hypoventilation syndrome. Am Rev Respir Dis.1993;147:1185-1191.
2.
Gozal D.Central congenital hypoventilation syndrome: an update. Pediatr Pulmonol. 1998;26:273-282.
3.
Haddad GG, Mazza NM, Defendini R., et al. Congenital failure of autonomic control of ventilation, gastric motility and heart rate. Medicine (Baltimore). 1978;57:517-526.
4.
Bolande RPNeurocristopathy: its growth and development in 20 years. Pediatr Pathol Lab Med. 1997;17:1-25.
5.
Amiel J., Laudier B., Attie-Bitach T., et al. Polyalanine expansion and frameshift mutations of the paired-like homeobox gene PHOX2B in congenital central hypoventilation syndrome. Nat Genet.2003;33:459-461.
6.
Weese-Mayer DE, Berry-Kravis EM, Zhou L., et al. Idiopathic congenital central hypoventilation syndrome: analysis of genes pertinent to early autonomic nervous system embryologic development and identification of mutations in PHOX2B. Am J Med Genet A. 2003;123:267-278.
7.
Young HM, Ciampoli D., Hsuan J., Canty AJExpression of Ret-, p75(NTR)-, Phox2a-, Phox2b-, and tyrosine hydroxylaseimmunoreactivity by undifferentiated neural crest-derived cells and different classes of enteric neurons in the embryonic mouse gut. Dev Dyn. 1999;216:137-152.
8.
Suita S., Taguchi T., Ieiri S., Nakatsuji T.Hirschsprung's disease in Japan: analysis of 3852 patients based on a nationwide survey in 30 years. J Pediatr Surg. 2005;40:197-201.
9.
Croaker GD, Shi E., Simpson E., Cartmill T., Cass DTCongenital central hypoventilation syndrome and Hirschsprung's disease. Arch Dis Child.1998;78:316-322.
10.
Kijima K., Sasaki A., Niki T., et al. Sudden infant death syndrome is not associated with the mutation of PHOX2B gene, a major causative gene of congenital central hypoventilation syndrome. Tohoku J Exp Med.2004;203:65-68.
